In situ expression of tumor antigens by messenger RNA-electroporated dendritic cells in lymph nodes of melanoma patients.

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Publication year
2009Author(s)
Source
Cancer Research, 69, 7, (2009), pp. 2927-34ISSN
Publication type
Article / Letter to editor

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Organization
Tumorimmunology
Medical Oncology
Paediatrics - OUD tm 2017
Dermatology
Pathology
Surgery
Nuclear Medicine
Journal title
Cancer Research
Volume
vol. 69
Issue
iss. 7
Page start
p. 2927
Page end
p. 34
Subject
N4i 4: Auto-immunity, transplantation and immunotherapy; NCMLS 2: Immune Regulation; NCMLS 6: Genetics and epigenetic pathways of disease; ONCOL 1: Hereditary cancer and cancer-related syndromes; ONCOL 2: Age-related aspects of cancer; ONCOL 3: Translational research; ONCOL 5: Aetiology, screening and detectionAbstract
Electroporation of dendritic cells (DC) with mRNA encoding tumor-associated antigens (TAA) for cancer immunotherapy has been proved efficient and clinically safe. It obviates prior knowledge of CTL and Th epitopes in the antigen and leads to the presentation of multiple epitopes for several HLA alleles. Here we studied the migration capacity and the antigen expression of mRNA-electroporated DC (mRNA-DC) in lymph nodes after vaccination in melanoma patients. DC were electroporated with mRNA encoding gp100 or tyrosinase, labeled with indium-111 and superparamagnetic iron oxide particles, and injected intranodally in melanoma patients 24 to 48 hours before scheduled dissection of regional lymph nodes. Immunohistochemical analysis of the lymph nodes after surgery revealed that mRNA-DC migrated from the injection site into the T-cell areas of the same and subsequent lymph nodes, where they expressed the antigen encoded by the electroporated mRNA. Furthermore, vaccine-related CD8(+) T-cell responses could be detected in 7 of 11 patients vaccinated with mRNA-DC. Together these data show that mature DC electroporated with mRNA encoding TAA migrate and express antigens in the lymph nodes and induce specific immune responses.
This item appears in the following Collection(s)
- Academic publications [227425]
- Electronic publications [107141]
- Faculty of Medical Sciences [86157]
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